Coffee consumption and CYP1A2 genotype in relation to bone mineral density of the proximal femur in elderly men and women: a cohort study

Hallström Helena, Melhus Håkan, Glynn Anders, Lind Lars, Syvänen Ann-Christine, Michaëlsson, Michaëlsson Karl

Description

Drinking coffee has been linked to reduced calcium conservation, but it is less clear whether it leads to sustained bone mineral loss and if individual predisposition for caffeine metabolism might be important in this context. Therefore, the relation between consumption of coffee and bone mineral density (BMD) at the proximal femur in men and women was studied, taking into account, for the first time, genotypes for cytochrome P450 1A2 (CYP1A2) associated with metabolism of caffeine. Methods Dietary intakes of 359 men and 358 women (aged 72 years), participants of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), were assessed by a 7-day food diary. Two years later, BMD for total proximal femur, femoral neck and trochanteric regions of the proximal femur were measured by Dual-energy X-ray absorptiometry (DXA). Genotypes of CYP1A2 were determined. Adjusted means of BMD for each category of coffee consumption were calculated. Results Men consuming 4 cups of coffee or more per day had 4% lower BMD at the proximal femur (p = 0.04) compared with low or non-consumers of coffee. This difference was not observed in women. In high consumers of coffee, those with rapid metabolism of caffeine (C/C genotype) had lower BMD at the femoral neck (p = 0.01) and at the trochanter (p = 0.03) than slow metabolizers (T/T and C/T genotypes). Calcium intake did not modify the relation between coffee and BMD. Conclusion High consumption of coffee seems to contribute to a reduction in BMD of the proximal femur in elderly men, but not in women. BMD was lower in high consumers of coffee with rapid metabolism of caffeine, suggesting that rapid metabolizers of caffeine may constitute a risk group for bone loss induced by coffee.

Informations

• Publié par: biomed
• Publié le: 01 janvier 2010
• Nombre de lectures: 24
• Langue: English

Extrait

Hallström et al. Nutrition & Metabolism 2010, 7:12
http://www.nutritionandmetabolism.com/content/7/1/12
RESEARCH Open Access
Coffee consumption and CYP1A2 genotype in
relation to bone mineral density of the proximal
femur in elderly men and women: a cohort study
1,6* 2,3 1 4 5 2,6Helena Hallström , Håkan Melhus , Anders Glynn , Lars Lind , Ann-Christine Syvänen , Karl Michaëlsson
Abstract
Background: Drinking coffee has been linked to reduced calcium conservation, but it is less clear whether it leads
to sustained bone mineral loss and if individual predisposition for caffeine metabolism might be important in this
context. Therefore, the relation between consumption of coffee and bone mineral density (BMD) at the proximal
femur in men and women was studied, taking into account, for the first time, genotypes for cytochrome P450 1A2
(CYP1A2) associated with metabolism of caffeine.
Methods: Dietary intakes of 359 men and 358 women (aged 72 years), participants of the Prospective Investigation
of the Vasculature in Uppsala Seniors (PIVUS), were assessed by a 7-day food diary. Two years later, BMD for total
proximal femur, femoral neck and trochanteric regions of the proximal femur were measured by Dual-energy X-ray
absorptiometry (DXA). Genotypes of CYP1A2 were determined. Adjusted means of BMD for each category of coffee
consumption were calculated.
Results: Men consuming 4 cups of coffee or more per day had 4% lower BMD at the proximal femur (p = 0.04)
compared with low or non-consumers of coffee. This difference was not observed in women. In high consumers
of coffee, those with rapid metabolism of caffeine (C/C genotype) had lower BMD at the femoral neck (p = 0.01)
and at the trochanter (p = 0.03) than slow metabolizers (T/T and C/T genotypes). Calcium intake did not modify
the relation between coffee and BMD.
Conclusion: High consumption of coffee seems to contribute to a reduction in BMD of the proximal femur in
elderly men, but not in women. BMD was lower in high consumers of coffee with rapid metabolism of caffeine,
suggesting that rapid metabolizers of caffeine may constitute a risk group for bone loss induced by coffee.
Introduction density (BMD) in both women [6-14] and men
Caffeine is the most widely used central nervous system [12,15-21] have been conflicting, which might be
stimulant in the world. There are several conceivable explained by differences in sample size, method of data
health benefits with the intake of caffeine-containing collection and amount of coffee consumed. In addition,
beverages but they can also produce unwanted health it has been suggested that a high caffeine intake is only
consequences. Caffeine increases calcium excretion [1-4] deleterious for bone health when calcium intake is low
and decreases intestinal calcium absorption [5], with 5 [22]. In Sweden, consumption of coffee and thus caf-
mg net loss of calcium per cup of coffee [1]. A high feine intake is high in a substantial proportion of the
intake of coffee could therefore also induce loss of bone population, making this setting suitable to study the
mineral. relation between coffee and BMD and subsequently the
Results from epidemiological studies investigating the risk of osteoporosis.
relation between coffee consumption and bone mineral Several enzymes are involved in the metabolism of
caffeine, but the most important is cytochrome P450
1A2(CYP1A2)[23].Thefirststepinthismetabolic
* Correspondence: [e-mail] 3pathway is a N -demethylation, which results in the for-1Research and Development Department, Toxicology Division, National Food
mation of 1,7-dimethylxanthine, i.e., paraxanthine [23].Administration, Box 622, SE-751 26 Uppsala, Sweden
© 2010 Hallström et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.Hallström et al. Nutrition & Metabolism 2010, 7:12 Page 2 of 9
http://www.nutritionandmetabolism.com/content/7/1/12
A wide variability in CYP1A2 activity between indivi- food diary after instructions from a dietician. The pre-
duals has been observed [24]. Depending on genotype, coded food diary had been prepared and previously used
some individuals are regarded as slow metabolizers of by the Swedish National Food Administration (NFA)
caffeine, while some are regarded as rapid metabolizers and Statistics Sweden in a food survey of 3,000 house-
[25,26]. There is also a gender difference with men, on holds in 1989 [30]. The questionnaire has been validated
average, having higher CYP1A2 activity [27]. To our [30,31]. The menu book included written instructions
knowledge, no study has yet investigated how coffee with an example on how to complete the book. The
consumption could affect BMD in relation to the rate of record sheets started with “day 1” followed by six addi-
caffeine metabolism determined by the genetic constitu- tional days. For each meal (breakfast, lunch, dinner and
tion of the individuals consuming coffee. However, in a snacks), the respondent was asked to specify where and
study of coffee intake, CYP1A2 genotype and risk of at what time the meal was eaten. The amounts con-
myocardial infarction coffee was associated with an sumed were reported in household measurements or
increased risk of nonfatal myocardial infarction only in specified as portion sizes according to a photograph
participants regarded as slow metabolizers of caffeine showing four portion sizes. Coffee and tea consumption
[26]. Accordingly, in the present study we hypothesize was registered six times daily (breakfast, lunch, supper,
that the participants’ genotype for cytochrome CYP1A2 between meals and in the evening).
could modify the relation between coffee consumption The daily intake of energy, caffeine, alcohol and
and BMD. This is because caffeine exposure of the body selected nutrients including calcium, vitamin D and A,
will last for longer periods in the “slow” caffeine meta- was calculated using a computerized program and infor-
bolizers than in the “rapid” caffeine metabolizers. Until mation about energy and nutrient contents of foods
now, however, the possibility of modulation by genotype from a database from the National Food Administration
for CYP1A2 has not been considered in studies of coffee that included 1,500 food items, drinks and recipes. Fil-
consumption and BMD. tered or brewed coffee is the most popular type of cof-
The principal aim of this study was to investigate the fee in the Nordic countries, while it should be noted
relation between consumption of coffee and BMD of the that decaffeinated coffee and tea are not typically con-
proximal femur in a population-based cohort of 70- sumed in the Swedish diet [23]. One cup of filtered cof-
year-old Swedish men and women. A secondary aim fee (150 mL) was estimated to contain approximately
was to study whether the relation between consumption 100 mg caffeine [23]. One cup of tea (200 mL) was esti-
of coffee and BMD in the cohort was modified by the mated to contain about 50 mg of caffeine [23]. No ana-
participants’ genotype for cytochrome P450 1A2 lyses of caffeine content of the consumed coffee and tea
(CYP1A2). were performed.
Materials and methods Measurement of bone mineral density at the proximal
Subjects femur
The Prospective Investigation of the Vasculature in On average, 2 years after the baseline investigation, 898
Uppsala Seniors (PIVUS) [28] has been described pre- of 1,016 cohort members agreed to undergo measure-
2viously [29]. In brief, all 70-year-old individuals residing ments of BMD (g/cm ) for total proximal femur,
in Uppsala, Sweden, in 2001-2004 were eligible. Of femoral neck and trochanteric regions of the proximal
these individuals, 2,025 were randomly selected and femur by DXA (DPX Prodigy, Lunar corp., Madison,
invited to participate within 2 months of their 70th WI, USA). This is the site of the most serious conse-
birthday from April 2001 to June 2004. Of those invited, quences of osteoporosis - the hip fracture [32], which
1,016 (50%) eventually participated in the study. The constitutes two main fracture categories: the femoral
participants were examined by measurements of blood neck and the trochanteric femoral fracture. When
pressure and anthropometry, blood sampling after an applicable, both extremities were used in the calculation.
overnight fast, routine medical history and assessment By triple measurements in 15 participants, the precision
of BMD using Dual-energy X-ray absorptiometry (DXA) error of the DXA measurements of total proximal femur
as described below. The study was approved by the in our laboratory has been calculated to be about 0.7%.
Ethics Committee of Uppsala University and all partici-
pants gave their written informed consent. Genotyping of CYP1A2
A common polymorphism in both Caucasians and
Dietary assessments Asians is the variation of the nucleotide at position -163
Dietary habits were registered in 850 (84%) of the parti- in intron 1 of the CYP1A2 gene. The C allele at position
cipants. Each participant recorded his or her food con- -163 in the CYP1A2 gene is considered to confer
sumption during 7 consecutive days using a pre-coded decreased inducibility to the enzyme [24,33,34]